Effects of dose-reduced Medac L-asparaginase on coagulation in trial ALL-BFM 2000

• Published in: Klinische Pädiatrie Vol. 215; no. 6; p. 321
• Main Authors: Attarbaschi, A, Mann, G, Kronberger, M, Witt, V, Gadner, H, Dworzak, M
• Format: Journal Article
• Language: English
• Published: Germany 01-11-2003
• Subjects: Adolescent; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - therapeutic use; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antithrombin III - analysis; Asparaginase - administration & dosage; Asparaginase - pharmacology; Blood Coagulation - drug effects; Blood Coagulation Tests; Child; Child, Preschool; Daunorubicin - administration & dosage; Daunorubicin - therapeutic use; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen - analysis; Glucocorticoids - administration & dosage; Glucocorticoids - therapeutic use; Humans; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Prospective Studies; Protein C - analysis; Protein S - analysis; Remission Induction; Time Factors; Vincristine - administration & dosage; Vincristine - therapeutic use
• ISSN: 0300-8630
• DOI: 10.1055/s-2003-45497

Glucocorticoids and L-asparaginase (L-ASP) are essential elements of contemporary chemotherapy of childhood acute lymphoblastic leukemia (ALL). Both cytotoxic drugs are well-known to induce significant alterations in hemostasis, especially affecting the inhibitors of coagulation including antithrombin III (AT III), protein C and protein S.
The objectives of the present prospective study were to analyze the course and degree of the changes of several coagulation proteins during induction therapy of 16 patients treated according to the Berlin-Frankfurt-Münster (BFM) ALL protocol 2000. The induction protocol included a 7-day mono-therapy with glucocorticoids followed by 4 weeks with additional vincristine, daunorubicin and E. coli L-ASP (Medac) which was administered at a dosage of 5000 IU/m (2) 8-times at 3-day intervals.
This analysis is the first to show that 5000 IU/m (2) of the Medac L-ASP leads to a less pronounced decrease of the plasma AT III and fibrinogen concentrations during induction therapy (after the 5 (th) L-ASP dose), as compared to previous BFM protocols which used the Medac L-ASP in a dosage of 10 000 IU/m (2). Our results confirmed that following a mono-therapy with glucocorticoids the AT III, protein C and protein S levels increased while the fibrinogen level decreased. As the D-Dimers remained within the normal range during the 3 weeks of L-ASP combination chemotherapy and none of the patients suffered a thromboembolic event, we also concluded that despite of the significant decrease of anticoagulant proteins, there might be a balance between coagulation and fibrinolysis; thus the D-Dimers may eventually serve as a helpful indicator for therapeutic interventions.